Asymptomatic red lesions
A fair-skinned man, age 60 years, presented after his wife noted blood spots on the inside of his undershirt. An asymptomatic lesion was discovered on his right upper back. This lesion was a 6 × 3.5 cm superficial papulosquamous plaque with an annular well-defined border, within which were scattered tiny focal areas of erosion. Dark red focal areas were found within the borders of the lesion. The lesion had been present for at least five years before it began to bleed. At no point had it been painful or itchy, and it had grown quite slowly.
A 27-year-old man was referred to the dermatology clinic for evaluation of an asymptomatic leg lesion. The lesion first appeared two years ago and doubled in size during that period. The patient's primary-care clinician had diagnosed the lesion as "ringworm" and psoriasis. Various creams, including a combination product containing betamethasone and clotrimazole, had had no effect. Additional history included newly diagnosed diabetes mellitus. No fever, cough, shortness of breath, or unexplained weight loss were reported.
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CASE #1: Superficial basal cell carcinoma
An antifungal cream/steroid combination prescribed earlier by the patient's primary-care clinician provided no beneficial effect. The man's skin was quite fair. An abundance of sun damage was noted, primarily on the patient's face and arms. He had a history of a number of sun-caused skin cancers, including basal cell carcinomas (BCCs).
Shave biopsy confirmed the expected diagnosis of superficial BCC. The most common treatment for superficial BCC is electrodessication and curettage, but this is not practical for such a large lesion. This procedure would result in a large raw area that would be painful and slow to heal. Pyogenic granuloma formation is a frequent complication associated with this treatment as well. Moreover, a large scar would certainly result, and the chance of recurrence with curettement of such a large lesion is all too high.1 Surgical excision of this lesion, with margins, would result in a scar roughly 3.5 times longer than the maximum dimension of the cancer; in this case, almost 1 ft long.2
Radiation therapy has long been used to good effect in individuals with BCCs. In actual practice, however, this treatment is usually reserved for recurrent or other aggressive tumors not amenable to surgical resolution.3 For many patients, radiation treatment is also impractical because it requires multiple visits over the course of several weeks (i.e., five sessions a week for four weeks).
Two of the most common topical medicines indicated in the treatment of superficial BCC are 5-fluorouracil (Carac, Efudex, Fluoroplex) cream or solution and imiquimod (Aldara) cream.4 The former is a pyrimidine analog that blocks DNA replication5 while the latter boosts the immune response to the cancer. Neither medication has been studied in cancers as big as this patient's.
Superficial BCC bears no resemblance to any of the other types of BCC. In fact, superficial BCC is often misdiagnosed as fungal infection, psoriasis or eczema.6 The most obvious clue to its identity is the fact that superficial BCC will almost always occur on sun-exposed skin of fair, sun-damaged individuals, typically on the back and shoulders and often in multiples.
Unlike psoriasis or eczema, superficial BCCs are fixed to the same location and grow slowly but steadily over several years' time. The annular, sharply defined palpable border — sometimes called "field fire" for its resemblance to the advancing border of a grass fire — is essentially pathognomonic.
While UV exposure is the most common cause of BCC, other triggers include arsenic exposure (mostly through groundwater contamination), coal, tar, ionizing radiation exposure, local trauma, vaccination and even tattooing.7-9 Geographic location, heredity and skin type are often involved as well.6
BCCs primarily appear on older patients (average age 67.5 years) because it typically takes 20 to 50 years from UV exposure to tumor genesis. However, BCCs are beginning to be seen on younger and younger patients — even in teenagers. Men are more than twice as likely as women to develop BCC. Patients aged 55 to 70 years are 100 times more likely to be diagnosed with BCC than an individual aged 20 years. Immunosuppression (as seen in HIV and transplant patients, for example) also increases risk.6
As for distribution, 70% of BCCs occur somewhere on the head (usually the face);10 25% on the trunk;11 and most of the rest on the hands, arms and legs. BCCs have been reported in non-sun-exposed areas, including axillae, and on genitials.12,13 At most, only about 0.1% metastasize,6 first to local nodes, then to the lungs, and finally to bones.
The predominant theory is that most BCCs develop from pluripotential cells in the basal layer of the epidermis or from certain parts of the follicular structure. In susceptible individuals, the hedgehog gene encodes an extracellular protein that binds to a cell membrane receptor complex, triggering a cascade of cellular events leading to cellular proliferation. Overexposure to UV radiation suppresses immunologic responsiveness to cutaneous tumors.
As mentioned, superficial BCCs do not resemble such far more common types as nodular or noduloulcerative tumors. These BCCs are familiar to most providers as a pearly papule or nodule. Other types of BCCs include sclerosing (scarlike) and pigmented types, which can be quite dark, especially in dark-skinned patients.
Some BCCs are more aggressive than others, as indicated by their clinical behavior and such histologic features as perineural involvement. Location — especially on the perinasilar and canthal areas of the face — can be associated with aggressive behavior and increased rates of recurrence. The superficial BCC in this case was so indolent as to be on the opposite end of the spectrum, requiring many years of neglect before becoming invasive.
Given the dearth of suitable treatment choices, the decision was made to begin the application of imiquimod 5% cream five days a week. The treatment is still in progress at this time. Such therapy will certainly cause irritation and weeping during the expected two-month treatment period but has a good chance of eradicating this lesion by promoting the production of cytokine precursors.
CASE #2: Necrobiosis lipoidica
In 1932, Urbach coined the term necrobiosis lipoidica diabeticorum to name the particular kind of plaques seen on the legs of diabetics. In 1935, Goldsmith was the first to note the appearance of the condition in individuals without diabetes.14 Twenty-five years later, Rollins and Winkleman analyzed a number of cases of this disease and again noted its presence in nondiabetics, leading them to suggest changing the name of the condition to necrobiosis lipoidica (NL), a term encompassing all cases of this clinical condition regardless of the presence or absence of diabetes.15
NL represents a disorder of collagen degeneration with a granulomatous response, eventuating clinically in the formation of shiny brown plaques that tend to enlarge slowly, becoming increasingly yellow in color with atrophic surfaces marked by telangiectasias on the periphery.14 Occurring mostly on the leg, the plaques average approximately 1 cm but can grow to many times that size. Multiple lesions are common, and relatively minor trauma to these lesions can result in erosions and ulcers that are difficult to treat.
As noted above, NL can occur in people without diabetes, but up to 60% of NL patients have been diagnosed with diabetes prior to the development of the plaques.14 Both diagnoses are made at the same time in 25% of cases, but the presence or progression of NL does not correlate with the severity of diabetes.14
The average age of development of NL is 30 years, but the range of ages varies a great deal. Women with NL outnumber men by at least 3:1.14
The clinical picture displayed by NL is clear enough to be essentially pathognomic, although biopsy is sometimes required to differentiate NL from such conditions as morphea, sarcoidosis, granuloma annulare, and xanthomata.14,16
Microscopically, NL demonstrates interstitial and palisaded granulomas in subcutaneous tissue as well as the dermis.14 In addition, blood vessel walls are thickened, and endothelial cells are swollen in the middle to deep dermis. In some cases, clinical correlation with microscopic findings is invaluable, especially with regard to possible granuloma annulare, NL's closest look-alike.
Fortunately, this patient's lesion and its clinical context were quite typical, permitting an empirical diagnosis and the initiation of treatment with topical steroid cream (fluocinonide 0.05%) b.i.d. Steroid creams can be useful in treating active, enlarging lesions but can be counterproductive in older, "burnt-out" lesions. Because the cause of the condition is unknown, treatment of NL can be problematic.
Arguably, the formation of traumatic ulcers in these lesions is the source of much difficulty.14 The prevention of trauma, with pressure stockings, and an assessment of the patient's living environment (for potential trauma from wheelchair parts or furniture, for example) are in order.
Many different treatment modalities have been used to treat NL with varying degrees of success. These include pentoxifylline (Pentopak, Pentoxil, Trental),17 photodynamic therapy,18 aspirin/dipyridamole (Permole, Persantine) combination,19 calcineurin inhibitors (e.g., tacrolimus [Hecoria, Prograf]),14 perilesional heparin injections,20 oral vitamin B, and tretinoin (Vesanoid),21 to name just a few.Joe Monroe, PA-C, is a physician assistant specializing in dermatology at Dawkins Dermatology in Oklahoma City.
1. James WD, Berger TG, Elston DM. "Dermatologic surgery." In: Andrews' Diseases of the Skin: Clinical Dermatology. 10th ed. Philadelphia, Pa.: Saunders-Elsevier; 2006:876.
2. Brownell I. "Nodular basal cell carcinoma." J Drugs Dermatol. 2007;6:1245-1246.
3. Mendenhall WM, Amdur RJ, Hinerman RW et al. "Radiotherapy for cutaneous squamous and basal cell carcinomas of the head and neck." Laryngoscope. 2009;119:1994-1999.
4. Geisse JK, Rich P, Pandya A et al. "Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: a double-blind, randomized, vehicle-controlled study." J Am Acad Dermatol. 2002;47:390-398.
5. Efudex (fluorouracil) [package insert]. Valeant Pharmaceuticals; 2005.
7. Cabrera HN, Gómez ML. "Skin cancer induced by arsenic in the water." J Cutan Med Surg. 2003;7:106-111.
8. Romão-Corrêa RF, Maria DA, Soma M et al. "Nucleolar organizer region staining patterns in paraffin-embedded tissue cells from human skin cancers. " J Cutan Pathol. 2005;32:323-328.
9. Keyhani K, Ashenhurst M, Oryschak A. "Periocular basal cell carcinoma arising in a site of previous trauma." Can J Ophthalmol. 2007;42:467-468.
10. Erba P, Farhadi J, Wettstein R et al. "Morphoeic basal cell carcinoma of the face." Scand J Plast Reconstr Surg Hand Surg. 2007;41:184-188.
11. Fresini A, Rossiello L, Severino BU et al. "Giant basal cell carcinoma." Skinmed. 2007;6:204-205.
12. Shindel AW, Mann MW, Lev RY et al. "Mohs micrographic surgery for penile cancer: management and long-term followup." J Urol. 2007; 178:1980-1985.
13. Mulvany NJ, Allen DG. "Differentiated intraepithelial neoplasia of the vulva." Int J Gynecol Pathol. 2008;27:125-135.
15. Rollins TG, Winkelmann RK. "Necrobiosis lipoidica granulomatosis. Necrobiosis lipoidica diabeticorum in the nondiabetic." Arch Dermatol. 1960;82:537-543.
16. Mistry N, Chih-Ho Hong H, Crawford RI. "Pretibial angioplasia: a novel entity encompassing the clinical features of necrobiosis lipoidica and the histopathology of venous insufficiency." J Cutan Med Surg. 2011; 15:15-20.
17. Littler CM, Tschen EH. "Pentoxifylline for necrobiosis lipoidica diabeticorum." J Am Acad Dermatol. 1987;17(2 Pt 1):314-316.
18. Heidenheim M, Jemec GB. "Successful treatment of necrobiosis lipoidica diabeticorum with photodynamic therapy." Arch Dermatol. 2006;142:1548-1550.
19. Eldor A, Diaz EG, Naparstek E. "Treatment of diabetic necrobiosis with aspirin and dipyridamole." N Engl J Med. 1978;298:1033.
20. Jetton RL, Lazarus GS. "Minidose heparin therapy for vasculitis of atrophie blanche." J Am Acad Dermatol. 1983;8:23-26.
21. Heymann WR. "Necrobiosis lipoidica treated with topical tretinoin." Cutis. 1996;58:53-54.
All electronic documents accessed May 15, 2012.